Reference SummaryMatsumoto M, J Environ Pathol Toxicol Oncol 2006;25(3):571-84

Title

Carcinogenicity and chronic toxicity of para-chloronitrobenzene in rats and mice by two-year feeding.

Authors

Matsumoto M; Aiso S; Senoh H; Yamazaki K; Arito H; Nagano K; Yamamoto S; Matsushima T

Journal

J Environ Pathol Toxicol Oncol

Volume

25

Issue

3

Year

2006

Pages

571-84

Abstract

Carcinogenicity and chronic toxicity of para-chloronitrobenzene (p-CNB) were examined by feeding diets containing p-CNB to rats and mice of both sexes for two years. The dietary concentration of p-CNB was 0 (control), 40, 200, or 1000 ppm (w/w) for rats and 0, 125, 500, or 2000 ppm for mice. Survival rates of the high-dosed male rats and male mice were significantly decreased compared with those of the respective controls, and this was attributed to the increased number of cancer deaths. Therefore, the high-dose levels were considered not to exceed the maximum tolerated dose. Significant decreases in red blood cell counts and hematocrit value and an increase in mean corpuscular volume were noted in the p-CNB-fed rats and mice. Nonneoplastic splenic lesions were characterized by capsule hyperplasia, fibrosis, fatty metamorphosis, and increased extramedullary hematopoiesis in rats, and congestion, increased extramedullary hematopoiesis, hemosiderin deposition, and ossification in mice. Incidences of fibromas, fibrosarcomas, osteosarcomas, sarcomas (NOS), and hemangiosarcomas in males and fibrosarcomas in females were significantly increased in the spleen of high-dosed rats. The most frequently observed splenic tumor was fibrosarcomas, followed by fibromas. The tumor incidences were increased in a dose-related manner and were more prevalent in males than in females. The malignant tumors metastasized mainly to the liver, peritoneum, and pancreas. Adrena/medullary hyperplasia and pheochromocytomas were significantly increased in the p-CNB-fed females. No tumor was induced in any of the p-CNB-fed mice of either sex except hepatic hemangiosarcomas in the 2000 ppm-fed females. Causative factors of p-CNB-induced carcinogenicity and chronic toxicity are discussed in light of the subchronic and chronic hematotoxicity reported in our present and previous studies and in the literature.

Links

J:120974 – MGI References
17073560 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
(C57BL/6NCrlj x DBA/2NCrlj)F1 Blood vessel hemangiosarcoma Liver

0 - 4

(C57BL/6NCrlj x DBA/2NCrlj)F1 Blood vessel hemangiosarcoma
  • para-chloronitrobenzene (p-CNB)
Liver

0 - 10

(C57BL/6NCrlj x DBA/2NCrlj)F1 Leukocyte - Lymphocyte lymphoma Lymph node

4 - 22

(C57BL/6NCrlj x DBA/2NCrlj)F1 Leukocyte - Lymphocyte lymphoma
  • para-chloronitrobenzene (p-CNB)
Lymph node

2 - 24

(C57BL/6NCrlj x DBA/2NCrlj)F1 Liver hepatocellular adenoma Liver

6 - 8

(C57BL/6NCrlj x DBA/2NCrlj)F1 Liver hepatocellular adenoma
  • para-chloronitrobenzene (p-CNB)
Liver

2 - 8

(C57BL/6NCrlj x DBA/2NCrlj)F1 Liver hepatocellular carcinoma Liver

2 - 4

(C57BL/6NCrlj x DBA/2NCrlj)F1 Liver hepatocellular carcinoma
  • para-chloronitrobenzene (p-CNB)
Liver

0 - 12

(C57BL/6NCrlj x DBA/2NCrlj)F1 Spleen hyperplasia Spleen

12

(C57BL/6NCrlj x DBA/2NCrlj)F1 Spleen hyperplasia
  • para-chloronitrobenzene (p-CNB)
Spleen

26 - 30

(C57BL/6NCrlj x DBA/2NCrlj)F1 Spleen lesion Spleen

0

(C57BL/6NCrlj x DBA/2NCrlj)F1 Spleen lesion
  • para-chloronitrobenzene (p-CNB)
Spleen

0

(C57BL/6NCrlj x DBA/2NCrlj)F1 Spleen tumor - nodular Spleen

1

(C57BL/6NCrlj x DBA/2NCrlj)F1 Spleen tumor - nodular
  • para-chloronitrobenzene (p-CNB)
Spleen

1 - 18